2. Academic Validation
  3. Novel tumor suppressor function of glucocorticoid-induced TNF receptor GITR in multiple myeloma

Novel tumor suppressor function of glucocorticoid-induced TNF receptor GITR in multiple myeloma

  • PLoS One. 2013 Jun 13;8(6):e66982. doi: 10.1371/journal.pone.0066982.
Yang Liu 1,  Phong Quang,  Esteban Braggio,  Hai Ngo,  Gayane Badalian-Very,  Ludmila Flores,  Yong Zhang,  Antonio Sacco,  Patricia Maiso,  Abdel Kareem Azab,  Feda Azab,  Ruben Carrasco,  Barrett J Rollins,  Aldo M Roccaro,  Irene M Ghobrial
Affiliations

Affiliation

  • 1 Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, United States of America.
PMID: 23785514 DOI: 10.1371/journal.pone.0066982
Abstract

Glucocorticoid-induced TNF Receptor (GITR) plays a crucial role in modulating immune response and inflammation, however the role of GITR in human cancers is poorly understood. In this study, we demonstrated that GITR is inactivated during tumor progression in Multiple Myeloma (MM) through promoter CpG island methylation, mediating gene silencing in primary MM plasma cells and MM cell lines. Restoration of GITR expression in GITR deficient MM cells led to inhibition of MM proliferation in vitro and in vivo and induction of Apoptosis. These findings were supported by the presence of induction of p21 and PUMA, two direct downstream targets of p53, together with modulation of NF-κB in GITR-overexpressing MM cells. Moreover, the unbalanced expression of GITR in clonal plasma cells correlated with MM disease progression, poor prognosis and survival. These findings provide novel insights into the pivotal role of GITR in MM pathogenesis and disease progression.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z